Histocompatibility genes, mapping to the major histocompatibility complex (MHC), code for cell membrane components which play a prominent role in the regulation of the immune response. MHC genes regulate lymphocyte collaboration, antigen presentation to effector lymphocytes, immune responsiveness, and susceptibility to neoplastic and immune diseases. The vast majority of information on the immunological function of the MHC has been obtained with the mouse MHC (H-2). Although the rat serves as the animal model for many human diseases, the susceptibility to which is regulated by MHC genes, research on the rat MHC, RT1, has not progressed extensively. The major effects of this proposal involve the comprehensive analysis of the RT1 complex and, in particular, RT1.B genes coding for Class II (Ia) antigens. Polymorphic RT1.B specificities will be serologically identified with (1) mouse Ia-specific alloantisera and monoclonal antibodies and (2) rat RT1.B-specific alloantisera and monoclonal antibodies. The RT1.B molecule origin of the defined specificities will be determined as well as their tissue distribution. The heterogeneity and cis-trans associations of polymorphic RT1.B molecule subunits will be investigated through increasingly sensitive biochemical assays, i.e., SDS-PAGE, two-dimensional gels and tryptic peptide maps. The RT1 linkage map will be delineated through the analysis of natural and selected intra-RT1 recombinants. Further, the proposed existence of a RT1-linked analog of the mouse suppressor T clel-expressed I-J subregion will be confirmed. The proposed studies will greatly advance the knowledge of the rat MHC as well the range of adaptation of mammalian MHC's in different species.